Interleukin-23 in the Pathogenesis of Inflammatory Bowel Disease and Implications for Therapeutic Intervention
| Autor: | Gavin W Sewell, Arthur Kaser |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Journal of Crohn's and Colitis. 16:ii3-ii19 |
| ISSN: | 1876-4479 1873-9946 |
| DOI: | 10.1093/ecco-jcc/jjac034 |
| Popis: | The interleukin-23 [IL-23] cytokine, derived predominantly from macrophages and dendritic cells in response to microbial stimulation, has emerged as a critical promoter of chronic intestinal inflammation. Genome-wide association studies linking variants in IL23R to disease protection, bolstered by experimental evidence from colitis models, and the successful application of therapies against the IL-12/IL-23 shared p40 subunit in the treatment of inflammatory bowel disease [IBD] all provide compelling evidence of a crucial role for IL-23 in disease pathogenesis. Moreover, targeting the p19 subunit specific for IL-23 has shown considerable promise in recent phase 2 studies in IBD. The relative importance of the diverse immunological pathways downstream of IL-23 in propagating mucosal inflammation in the gut, however, remains contentious. Here we review current understanding of IL-23 biology and explore its pleiotropic effects on T cells, and innate lymphoid, myeloid and intestinal epithelial cells in the context of the pathogenesis of IBD. We furthermore discuss these pathways in the light of recent evidence from clinical trials and indicate emerging targets amenable to therapeutic intervention and translation into clinical practice. |
| Databáze: | OpenAIRE |
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